Nrtis (Includes AccessPak for HIV PEP Basic) ↔ Hepatotoxicity

Severe Potential Hazard, Moderate plausibility

Applies to: Alcoholism, Liver Disease

Hepatotoxicity including lactic acidosis, severe hepatomegaly with steatosis, fulminant hepatitis, and hepatic failure has rarely been associated with the use of nucleoside reverse transcriptase inhibitors (NRTIs) alone or in combination with other antiretroviral agents. Therapy with NRTIs should be administered cautiously in patients with preexisting liver disease, a history of alcohol abuse, or hepatitis. Therapy should be suspended if clinical or laboratory findings suggestive of lactic acidosis or pronouced hepatotoxicity occur.

Tenofovir (Includes AccessPak for HIV PEP Basic) ↔ Renal Dysfunction

Severe Potential Hazard, High plausibility

Applies to: Renal Dysfunction

Tenofovir is primarily eliminated by the kidney via glomerular filtration and active tubular secretion. Renal impairment, including acute renal failure and Fanconi syndrome, has been reported with tenofovir use. Close monitoring of renal function and lengthening the dosing interval are recommended for patients with creatinine clearance less than 50 mL/min. Creatinine clearance should be calculated in all patients before starting tenofovir treatment and during treatment when clinically appropriate. Routine monitoring of serum creatinine and phosphorus is recommended for patients at risk of or with a history of renal dysfunction. Safety and effectiveness have not been evaluated in patients with renal insufficiency using dose adjustments; therefore, the benefit of tenofovir treatment should be weighed against the risk of renal toxicity. Tenofovir should be avoided in patients who are currently using or have recently used nephrotoxic drugs.

References

Emtricitabine (Includes AccessPak for HIV PEP Basic) ↔ Hemodialysis

Moderate Potential Hazard, High plausibility

Applies to: hemodialysis

Emtricitabine is removed by hemodialysis. Following an emtricitabine dose administered 1.5 hours before the hemodialysis session, approximately 30% of the dose was removed over three hours of hemodialysis (blood flow rate of 400 mL/min and a dialysate flow rate of 600 mL/min). Emtricitabine should be administered after hemodialysis.

Emtricitabine is primarily eliminated by the kidney. Compared to patients with normal renal function (CrCl above 80 mL/min), peak plasma concentration (Cmax) and systemic exposure (AUC) of emtricitabine increased by 45% and 113%, respectively, in patients with moderate renal dysfunction (CrCl 30 to 49 mL/min), and 27% and 186%, respectively, in patients with severe renal dysfunction (CrCl below 30 mL/min). Systemic exposure was increased even further in patients with end-stage renal disease managed on dialysis. These patients had an approximately 3.5-fold increase in emtricitabine AUC compared to patients with normal renal function. Renal clearance of emtricitabine decreased by 68% and 86%, respectively, in patients with moderate and severe renal dysfunction. Dosage adjustment of emtricitabine is recommended for patients with CrCl below 50 mL/min, including patients on dialysis, in accordance with the manufacturer's product labeling. Clinical response to treatment and renal function should be closely monitored.

References

Tenofovir (Includes AccessPak for HIV PEP Basic) ↔ Bone Toxicity

Moderate Potential Hazard, Moderate plausibility

Applies to: Osteoporosis, Vitamin D Deficiency

Osteomalacia and reduced bone mineral density have been reported in animal toxicology studies involving tenofovir exposures 6- to 12-fold those observed in humans. The mechanism of bone toxicity has not been established, and it is not known if long-term use of tenofovir disoproxil fumarate will cause bone abnormalities in humans.

References

Tenofovir (Includes AccessPak for HIV PEP Basic) ↔ Liver Disease

Minor Potential Hazard, Low plausibility

Applies to: Liver Disease

There are no data concerning the use of tenofovir disoproxil fumarate in patients with hepatic impairment. Tenofovir and tenofovir disoproxil are not metabolized by liver enzymes. However, since tenofovir is not entirely eliminated by the kidney (70% to 80%), tenofovir pharmacokinetics may be altered in patients with impaired hepatic function.

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